摘要目的 观察人参皂苷Rb1对肠缺血再灌注致肾损伤的影响及机制.方法 将48只成年雄性C57BL/6J小鼠随机分为4组(n=12):假手术组(S组)、肠缺血再灌注组(ⅡR组)、Rb1低剂量组(Rb1-30组)、Rb1高剂量组(Rb1-60组).采用小鼠肠缺血再灌注模型.Rb1-30组和Rb1-60组分别于再灌注前腹腔给予30、60 mg/kg的Rb1.再灌注2h时心脏采血检测血尿素氮(BUN)、肌酐(Cr)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL),观察肾脏病理学改变,检测肾组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量及Western blot检测血红素氧合酶-1(HO-1)、NF-E2相关因子(Nrf2)蛋白表达.结果 ⅢR组(HO-1:4.03±0.60,Nrf2:3.42 ±0.47)高于S组(HO-1:1.50±0.16,Nrf2:0.61 ±0.14)(P＜0.01),而Rh1-30组(HO-1:8.78±1.12,Nrf2:6.02±0.55)和Rb1-60组(HO-1:15.76±1.33,Nrf2:8.29±0.66)较ⅢR组进一步增高(P＜0.05).与S组(16.70 ±4.06)比较,ⅡR组(198.60±9.71)中肾损伤程度增高(P＜0.01),血清BUN(21.55±1.50)、Cr(20.65±1.53)和NGAL(155.93±8.07)水平、肾组织MDA(5.00±1.53)含量升高而SOD(9.49±1.39)活性降低(P＜0.01).与ⅡR组比较,Rb1-60组(94.60±9.24)中肾损伤程度减轻(P＜0.05),BUN(Rb1-30:15.52±1.23;Rb1-60:12.91±1.41)、Cr(Rb1-30: 16.00±1.50;Rb1-60: 13.14±1.22)和NGAL(Rb1-30:124.44±6.52;Rb1-60:101.76±12.20)水平、肾组织MDA(Rb1-30:4.12±0.47;Rb1-60:3.22±0.54)含量降低而SOD(Rb1-30:14.77±1.87;Rb1-60:18.91±1.56)活性升高(P＜0.01).结论 肠缺血再灌注可致肾损伤,人参皂苷Rb1通过激活Nrf2/ARE通路,诱导HO-1表达,从而减轻肠缺血再灌注所致肾损伤.

abstractsObjective To investigate the effects of ginsenoside Rb1 on acute renal injury induced by intestinal ischemia reperfusion (ⅡR) in mice.Methods Forty-eight male C57BL/6J mice were randomly divided into four groups (n =12) : sham group, IIR group, 30 mg/kg ginsenoside Rb1 (Rb1-30) group, and 60 mg/kg ginsenoside Rb1 (Rb1-60) group.Intestinal ischemia reperfusion model in mice was established.30 mg/kg and 60 mg/kg ginsenoside Rb1 were given intraperitoneally in Rb1-30 group and Rb1-60 group respectively before reperfusion.After 2 h reperfusion, blood urea nitrogen (BUN), creatinine (Cr), and neutrophil gelatinase associated lipocalin (NGAL) levels in serum were measured.Renal histological changes were observed and evaluated.Superoxide dismutase (SOD) and malondialdehyde (MDA) levels in renal tissues were detected.Western blotting was used to observe the expression levels of NF and E2 related factor (Nrf2) and heme oxygenase-1 (HO-1) in renal tissues.Results The expression levels of HO-1 and Nrf2 in ⅡR group (4.03 ±0.60 and 2:3.42 ±0.47) were significantly higher than those in S group (1.50 ±0.16 and 2:0.61 ±0.14) (P＜0.01), and those in RB-30 group (8.78 ± 1.12 and 2:6.02 ±0.55) and RB-60 group (15.76 ± 1.33 and 8.29 ±0.66) were significantly higher than those in ⅡR group (P ＜0.05).ⅡR-induced renal injury in ⅡR group (198.60 ± 9.71) was significantly aggravated as compared with S group (16.70 ±4.06) (P ＜0.01).In ⅡR group, BUN (21.55 ±1.50) , Cr (20.65 ± 1.53) and NGAL (155.93 ±8.07) in serum and MDA (5.00 ± 1.53, P ＜0.01) in the renal tissues were increased and SOD (9.49 ± 1.39) decreased (P ＜ 0.01) as compared with S group.Ginsenoside Rb1 (30, 60 mg/kg) could alleviate renal injury (Rb1-30: 135.10±8.71;Rb1-60: 94.60 ±9.24, P＜0.01), decrease BUN (Rb1-30:15.52 ± 1.23;Rb1-60:12.91 ±1.41), Cr (Rb1-30: 16.00±1.50;Rb1-60: 13.14±1.22) and NGAL (Rb1-30: 124.44±6.52;Rb1-60:101.76 ± 12.20) in serum, MDA level (Rb1-30: 4.12 ±0.47;Rb1-60: 3.22 ±0.54) (P ＜0.01) in the renal tissues, and increase SOD level (Rb1-30: 14.77 ± 1.87;Rb1-60: 18.91 ± 1.56) (P ＜0.01).Conclusion Ginsenoside Rb1 attenuated acute renal injury induced by IIR by activating Nrf2/ARE pathway and upregulating the protein expression of HO-1.